Space, energy and synthetic half-reactions

For as long as I can remember, I have been fascinated by the periodic table of elements and how it relates chemical properties to an element’s position in the table. Its predictive applications and its ability to teach us some of the principles behind chemical transformations are far-reaching and cannot be overestimated.

At the same time, chemical reactivity is much more nuanced than might be gleaned by looking at the rows and periods of Mendeleev’s venerable classification. For example, carbon participates in an overwhelmingly diverse set of chemical transformations, yet relatively little can be concluded about carbon’s context-dependent reactivity by looking at the periodic table alone. So what is the most appropriate means to classify organic transformations?

The prevailing approach, prescribed by most textbooks, centres on functional groups. This method builds on sameness and categorises reactions based on the expected reactivity of atoms in particular environments. But this classification is not optimally conducive to predicting reaction outcomes and establishing the mechanism by which they proceed. While modern theoretical methods based on quantum mechanics are demonstrably appropriate at suggesting detailed ab initio explanations to countless molecular-level phenomena, there might be benefits to a simple structure-driven formalism that builds on reactivity’s foundation: the driving force that is needed to run energetically uphill steps. Securing an appropriate match between the driving force and the reactive intermediate that needs to be created or channelled in a particular direction is what chemical reactivity is all about.